The broad objective of this research plan is to investigate the control of several cell- or organ-specific functions in established clonal strains of differentiated mammalian cells in culture. Studies will focus on hormone-producing, hormone-responsive pituitary cell strains (GH-cells). The methods to be used include biochemical, immunologic, cytologic, electrophysiologic and genetic techniques. Five specific objectives will be examined. 1. Plasma membrane receptors on GH-cells for 3 regulatory peptides (thyrotropin-releasing hormone, TRH; somatostatin, SRIH: and epidermal growth factor, EGF) will be characterized. Emphasis will be on the mechanisms regulating the concentrations and affinities of each receptor by homologous and heterologous ligands. 2. The mechanisms of the acute actions of TRH, SRIH and EGF on GH-cells will be studied. The roles of ion fluxes, protein phosphorylation, and electrophysiologic events in prolactin and growth hormone release will be examined. 3. Acute inibition of ACTH release by glucocorticoid hormones will be investigated in AtT 20/D16 cells. 4. It will be determined whether the same GH-cell produces both growth hormone and prolactin simultaneously. 5. The actions of tumor promoters (such as the phorbol diesters) on differentiated functions in cultured cells will be examined with an emphasis on membrane alterations. The experiments proposed take advantage of several unique properties of tumor cells in culture and permit studies that would be difficult or impossible to perform otherwise. Available evidence indicates that many of the mechanisms elucidated in these neoplastic cells also apply to normal cells.